Abstract 10333: Expression of Phospholipase A2 Groups IIE and V was Associated With the Development of Calcification and the Upregulated Expression of Osteogenic Molecules in Human Aortic Valves
Pro-inflammatory eicosanoids and fatty acids may play pathogenic roles in aortic valve calcification. These lipid mediators are produced by hydrolysis of membrane phospholipids via phospholipases A2 (PLA2). We examined if PLA2s are expressed in human aortic valves and if PLA2s expression are related to the expression of calcification-related proteins in human aortic valves.
Methods and Results: This study included 38 non-rheumatic aortic valves obtained at cardiac valve-replacement surgery. The presence of PLA2 groups IB, IID, IIE, IIF, III, IV, V, VI, X and XIIA was assessed by immunohistochemical analysis. Immunoreactivity of these PLA2s was found in nucleated cells and extracellular spaces. Expression of PLA2 groups IB, IIE, III and V was highly prevalent (20 - 90% of nucleated cells), while that of the other PLA2s was low (< 10% of nucleated cells). There were significant and positive correlations between percentages of areas that were immune-positive for PLA2-IIE or -V and grade of calcification (r = 0.60 and 0.43, respectively, p < 0.01). Percentages of areas immuno-positive for PLA2-IIE or -V were positively correlated with expression of pro-osteogenic molecules BMP-2 (r = 0.58 and 0.68, respectively, p < 0.01), osteopontin (r = 0.43 and 0.37, p < 0.05) and ALP (r = 0.29 and 0.14, p < 0.05). Similarly, RT-PCR studies showed that expression of mRNAs for PLA2-IIE or -V was significantly and positively correlated with mRNAs for BMP-2, osteopontin and ALP (p < 0.05 in all). Immunoreactivity of COX-1, COX-2 and 5-LOX, downstream enzymes of PLA2 for the arachidonic acid cascade, was co-localized with that of PLA2-IIE and -V in valve interstitial (VI) cells expressing α-SMA and macrophages expressing CD68. In in-vitro experiments using cultured VI cells obtained from human aortic valves, expression of mRNAs for BMP-2, osteopontin and ALP was suppressed by inhibiting expression of PLA2-IIE or -V with specific siRNAs.
Conclusions: Expression of PLA2-IIE and -V was associated with development of calcification and increased expression of pro-osteogenic molecules in human aortic valves. Inhibition of these PLA2s suppressed induction of osteogenic molecules in cultured cells. PLA2-IIE and -V might play roles in the pathogenesis of valve calcification.
- © 2013 by American Heart Association, Inc.